What Information on Impurities is necessary for a Marketing Authorisation Application for a generic Medicinal Product in the US?

"Guidance for Industry - ANDAs: Impurities in Drug Products" - this is the title of the new Guidance the FDA issued end of November. This document replaces the identical Guidance from 1998. It was updated with the purpose to match it more with the contents of the ICH Q3B(R2) Guideline "Impurities in New Drug Products".

The document describes the information with regard to impurities from degradation products in a marketing authorisation application for a generic medicinal product the FDA expects. The applicant needs to create a list of impurities which is based on the commercial manufacturing process described in the dossier and the degradation products proven there. The Guidance mentions "specified degradation products" that can be identified or not identified and recommends to list both types of degradation products in the authorisation dossier.

The Guidance answers the question regarding the qualification of the degradation products with the requirement that the applicant has to indicate a rationale for the acceptance criteria which particularly has to consider security aspects regarding the genotoxic potential as well. At the end of the document a decision tree provides some support for the identification and qualification of degradation products in generic medicinal products. This decision tree widely resembles the one in the ICH Guideline Q3B(R2) and also comprises recommendations, to consider studies on the general and on genotoxicity.

With the - already overdue - revision of this already 12 years old Guidance the FDA adapts to the European regulation standard with regard to impurities in generic medicinal products. Applicants for authorisation striving to market generic medicinal products on the US market can now rely on a regulation that is largely harmonised with that in Europe.